This project has two specific aims: (1) the development of simple new antitumor agents related to azuloquinones and (2) an understanding of the physical and chemical consequences of cyclic conjugation in the azuloquinones, a novel class of bicyclic nonbenzenoid quinones. The research will require considerable synthetic organic chemistry. During the first two years of this program, several derivatives of azulene hydroquinones were synthesized and found to exhibit significant cytotoxic activity. The most active compounds have been submitted for testing against P-388 leukemia in mice. While these tests are underway, other potential antitumor compounds will be synthesized, based on the structure-activity relationships which have already begun to emerge. The simple molecular structures of these new cytotoxic compounds and the relative ease with which they can be prepared and modified make the family of oxygenated azulenes especially attractive as a starting point for antitumor drug development. In addition, the azuloquinones belong to the little-known and poorly-understood class of bicyclic compounds characterized by two nonbenzenoid cyclic pi-systems sharing a common side. An extensive theoretical analysis of the eleven possible quinones of azulene (all then unknown) was completed during the first two years of this program, and predictions were made about many of their physical and chemical properties. Those which have now been synthesized are unstable, as predicted. Future research will focus on: (1) the synthesis of those azuloquinones predicted to exhibit the greatest stability, (2) generation of the more reactive isomers for study at low temperatures, and (3) stabilization of the more reactive azuloquinones by substituent effects. A variety of physical and chemical studies will be used to reveal the special consequences of cyclic conjugation in these new compounds.